A major clinicoepidemiological program associated with Herpes simplex viruses (HSV) is that of recurrent infection. Current evidence indicate one of the major problems for latency in-between recurrences is the sensory ganglia. The studies are aimed at obtaining further understanding of the basic mechanisms of HSV-1 latency in human trigeminal ganglia and developing a more natural model for an HSV-like virus in an animal. For the latter purpose, feline rhinotracheitis virus is being used in cats to study its neurobiology, including establishment of latency and reactivation, virus transport and electrophysiological changes. Because a common denominator for HSV reactivation triggers may be prostaglandins and cyclic nucleotides, studies in humans include assays of these chemicals in the blood at the onset of recurrences and in intervening times. Prostaglandins and cyclic nucleotides will be measured in the human ganglia, with or without latent virus, and inhibitors of these chemicals will be used to determine their effect on virus reactivation. Attempts are also being made to obtain single cell type preparations to define and enumerate the cells harboring the virus and for the biochemical studies. The long-term goal is to find some means of preventing HSV recurrences which afflict at least one-third of our population and may be associated occasionally with severe psychological and physical problems.